1. Field of the Invention
The present invention relates to new hexahydropyrano [3, 2-b] [1, 4] benzothiazine derivatives and pharmaceutically acceptable acid-addition salts thereof. Further, the present invention relates to agents for activating brain metabolism and improving cerebral function comprising an effective amount of a hexahydropyrano [3, 2-b] 1, 4] benzothiazine derivative or a pharmaceutically acceptable acid-addition salt thereof.
2. Description of the Prior Art
Patients suffering from senile dementia increase in number every year to become a social problem. The clinical symptoms of senile dementia comprise the nucleus of symptoms such as defects of memory, disorientation, understanding and judgment troubles and attendant mental symptoms such as depression, night delirium, delusion and hallucination, and emotional indifference. Although conventional agents for activating brain metabolism and for improving cerebral function are effective on improvement of attendant mental symptoms of senile dementia, these agents are not effective on improvement of nucleus symptoms. According to the study of a synapse level of memory, it suggests that a calcium signal and protein kinase C play an important role in the bases of processes of memory [Lynch and Baudry, Science, vol. 224, pp. 1057-1063 (1984); Akers et al., Science, vol. 231, pp. 587-589 (1986); Alkon, Scientific American, vol. 261, pp. 42-50 (1989); Olds et al., Science, vol. 245, pp. 866-869 (1989)]. It becomes clear that release of calcium and activation of protein kinase C are caused by inositol 1,4, 5-trisphosphate, which are produced by hydrolysis of phosphatidyl inositol 4, 5-diphosphate of an inositol phospholipid, and diacylglycerol. [Berridge and Irvine, Nature, vol. 312, pp. 315-321 (1984); Nishizuka, Science, vol. 233, pp. 305-312 (1986)]. Accordingly, materials for facilitating metabolic turnover of the inositol phospholipid of a hippocampus associated with memory are expected as a medicine for improving a deficit of cerebral function, which is nucleus symptoms of dementia, and it is desired to develop such chemicals.